The objective of this research is to study the intracellular effects of alcohol and its metabolites on selected CNS cultures, in order to evaluate specific subcellular alterations and in an attempt to relate these alterations to changes in the formation and metabolism of biogenic amines and cyclic AMP. In ethanol intoxication, clinical and pharmacological evidence point to the likelihood of selective vulnerability of cerebellar and hypothalamic neurons, and pharmacological studies have suggested a possible role played by alterations in brain biogenic amines. It is intended to establish suitable developing and mature cultures of newborn mouse cerebellum and hypothalamus, to which will be added various concentrations of ethanol and its derivative, acetaldehyde, for periods ranging from 12 hours to 60 days. Specific attention will be given to changes in cellular organelles, including smooth reticulum, mitochondria, synaptic vesicles and dense-core vesicles. The approach will include light and electron microscopy, and, where necessary, enzyme cytochemistry and histochemistry. Attempts will be made to correlate the intracellular changes with metabolic studies of biogenic amines (such as 5-HT and norepinephrine) and cyclic AMP in the same systems. Intracellular effects of ethanol in vivo in the CNS of mice exposed to ethanol vapors are also being studied.